The human adenovirus, particularly the well characterized Ad 2, provides excellent model systems to investigate both viral replication and eukaryotic cell molecular biology. Predominantly cellular enzymes are used for viral DNA replication, RNA transcription and processing, and protein synthesis. Furthermore, the function of a single viral gene can transform a cell to malignancy. Our long-range goals are to achieve a complete understanding of the mechanisms of viral replication, cell transformation, and eukaryotic cell biology. Specifically we will study: (a) viral DNA repication and structures; (b) viral RNA transcription, processing, and methylation; (c) viral protein synthesis; (d) viral conditional-lethal mutants; (e) viral-specific macromolecular synthesis in transformed cell. In addition, we will isolate and functionally characterize in vitro viral specific macromolecules from productive infections and transformed cells.